Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.

Detalhes bibliográficos
Autor(a) principal: Naumann, Gustavo Baptista
Data de Publicação: 2011
Outros Autores: Silva, Liliana F., Silva, Luciana Maria, Faria, Gilson, Richardson, Michael, Evangelista, Karla, Kohlhoff, Markus, Gontijo, Celia Maria Ferreira, Navdaev, Alexei, Rezende, Flavia F. de, Eble, Johannes, Sanchez, Eladio Oswaldo Flores
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/8991
Resumo: Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil
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spelling Naumann, Gustavo BaptistaSilva, Liliana F.Silva, Luciana MariaFaria, GilsonRichardson, MichaelEvangelista, KarlaKohlhoff, MarkusGontijo, Celia Maria FerreiraNavdaev, AlexeiRezende, Flavia F. deEble, JohannesSanchez, Eladio Oswaldo Flores2014-11-28T11:54:40Z2014-11-28T11:54:40Z2011NAUMANN, Gustavo Baptista et al. Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom. Biochim Biophys Acta, v. 1810, n. 7, p. 683-694, 2011.0006-3002https://www.arca.fiocruz.br/handle/icict/899110.1016/j.bbagen.2011.04.003engElsevierCytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrasilFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, BrasilFrankfurt University Hospital. Center for Molecular Medicine. Dept. Vascular Matrix Biology Excellence Cluster CardioPulmonary System. Frankfurt , GermanyFrankfurt University Hospital. Center for Molecular Medicine. Dept. Vascular Matrix Biology Excellence Cluster CardioPulmonary System. Frankfurt , GermanyFrankfurt University Hospital. Center for Molecular Medicine. Dept. Vascular Matrix Biology Excellence Cluster CardioPulmonary System. Frankfurt , GermanyFundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, BrazilBackground : Multifunctional l-amino acid oxidases (LAAOs) occur widely in snake venoms. Methods : The l-AAO from Bothrops leucurus (Bl-LAAO) venom was purified using a combination of molecular exclusion and ion-exchange chromatographies. We report some biochemical features of Bl-LAAO associated with its effect on platelet function and its cytotoxicity. Results: Bl-LAAO is a 60 kDa monomeric glycoprotein. Its N-terminal sequence shows high homology to other members of the snake-venom LAAO family. Bl-LAAO catalyzes oxidative deamination of l-amino acids with the generation of H2O2. The best substrates were: l-Met, l-Norleu, l-Leu, l-Phe and l-Trp. The effects of snake venom LAAOs in hemostasis, especially their action on platelet function remain largely unknown. Bl-LAAO dose-dependently inhibited platelet aggregation of both human PRP and washed platelets. Moreover, the purified enzyme exhibited a killing effect in vitro against Leishmania sp., promastigotes, with a very low EC50 of 0.07 μM. Furthermore, the cytotoxicity of Bl-LAAO was observed in the stomach cancer MKN-45, adeno carcinoma HUTU, colorectal RKO and human fibroblast LL-24 cell lines. The enzyme released enough H2O2 in culture medium to induce apoptosis in cells in a dose- and time-dependent manner. The biological effects were inhibited by catalase. Conclusion: Bl-LAAO, a major component of B. leucurus venom, is a cytotoxin acting primarily via the generation of high amounts of H2O2 which kill the cells. General significance: These results allow us to consider the use of LAAOs as anticancer agents, as tools in biochemical studies to investigate cellular processes, and to obtain a better understanding of the envenomation mechanism.Animal toxinBl-LAAOamino acid oxidasePlatelet functionApoptosisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8991/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALCytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.pdfCytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.pdfapplication/pdf1756940https://www.arca.fiocruz.br/bitstream/icict/8991/2/Cytotoxicity%20and%20inhibition%20of%20platelet%20aggregation%20caused%20by%20an%20l-amino%20acid%20oxidase%20from%20Bothrops%20leucurus%20venom.pdfcea9e0c6ac23255a10470abd5f8dade0MD52TEXTCytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.pdf.txtCytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.pdf.txtExtracted texttext/plain60252https://www.arca.fiocruz.br/bitstream/icict/8991/3/Cytotoxicity%20and%20inhibition%20of%20platelet%20aggregation%20caused%20by%20an%20l-amino%20acid%20oxidase%20from%20Bothrops%20leucurus%20venom.pdf.txtd6214bf63d66044313ecab72b06890d0MD53icict/89912019-06-19 10:13:25.157oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:13:25Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
title Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
spellingShingle Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
Naumann, Gustavo Baptista
Animal toxin
Bl-LAAO
amino acid oxidase
Platelet function
Apoptosis
title_short Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
title_full Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
title_fullStr Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
title_full_unstemmed Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
title_sort Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom.
author Naumann, Gustavo Baptista
author_facet Naumann, Gustavo Baptista
Silva, Liliana F.
Silva, Luciana Maria
Faria, Gilson
Richardson, Michael
Evangelista, Karla
Kohlhoff, Markus
Gontijo, Celia Maria Ferreira
Navdaev, Alexei
Rezende, Flavia F. de
Eble, Johannes
Sanchez, Eladio Oswaldo Flores
author_role author
author2 Silva, Liliana F.
Silva, Luciana Maria
Faria, Gilson
Richardson, Michael
Evangelista, Karla
Kohlhoff, Markus
Gontijo, Celia Maria Ferreira
Navdaev, Alexei
Rezende, Flavia F. de
Eble, Johannes
Sanchez, Eladio Oswaldo Flores
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Naumann, Gustavo Baptista
Silva, Liliana F.
Silva, Luciana Maria
Faria, Gilson
Richardson, Michael
Evangelista, Karla
Kohlhoff, Markus
Gontijo, Celia Maria Ferreira
Navdaev, Alexei
Rezende, Flavia F. de
Eble, Johannes
Sanchez, Eladio Oswaldo Flores
dc.subject.en.pt_BR.fl_str_mv Animal toxin
Bl-LAAO
amino acid oxidase
Platelet function
Apoptosis
topic Animal toxin
Bl-LAAO
amino acid oxidase
Platelet function
Apoptosis
description Fundação Ezequiel. Centro de Pesquisa e Desenvolvimento. Belo Horizonte, MG, Brazil
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2014-11-28T11:54:40Z
dc.date.available.fl_str_mv 2014-11-28T11:54:40Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv NAUMANN, Gustavo Baptista et al. Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom. Biochim Biophys Acta, v. 1810, n. 7, p. 683-694, 2011.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/8991
dc.identifier.issn.none.fl_str_mv 0006-3002
dc.identifier.doi.none.fl_str_mv 10.1016/j.bbagen.2011.04.003
identifier_str_mv NAUMANN, Gustavo Baptista et al. Cytotoxicity and inhibition of platelet aggregation caused by an l-amino acid oxidase from Bothrops leucurus venom. Biochim Biophys Acta, v. 1810, n. 7, p. 683-694, 2011.
0006-3002
10.1016/j.bbagen.2011.04.003
url https://www.arca.fiocruz.br/handle/icict/8991
dc.language.iso.fl_str_mv eng
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dc.publisher.none.fl_str_mv Elsevier
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